Antibacterial Oligomeric Polyphenols from the Green Alga Cladophora socialis

• Type of Material: Article
• Authors: Serge Lavoie, Georgia Institute of Technology; Anne Marie Sweeney-Jones, Georgia Institute of Technology; Nazia Mojib, Georgia Institute of Technology; Brandon Dale, Emory University; Kerstin Gagaring, Scripps Research Institute; Case W. McNamara, Scripps Research Institute; Cassandra Quave, Emory University; Katy Soapi, University of the South Pacific; Julia Kubanek, Georgia Institute of Technology
• Language: English
• Date: 2019-05-03
• Publisher: Hans Publishers (汉斯出版社)
• Publication Version: Final Published Version
• Copyright Statement: © 2019 American Chemical Society.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.joc.8b03218
• Title of Journal or Parent Work: Journal of Organic Chemistry Research
• ISSN: 2330-5231
• Volume: 84
• Issue: 9
• Start Page: 5035
• End Page: 5045
• Grant/Funding Information: This work was supported by ICBG Grant U19-TW007401 and by NIAID Grant R21 AI136563 from the U.S. National Institutes of Health and the Bill & Melinda Gates Foundation, Seattle, WA (Grant No. OPP1107194).; This research was supported in part through research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at the Georgia Institute of Technology, Atlanta, GA.
• Keywords: Fijian green alga; oligomeric phenols; overlapping aromatic signals; cladophora socialis; Gram-positive; DFT calculations; picric acid; Gram-negative; NMR spectroscopy; biphenyl; tetrahydroxy; cladophorols; synthesized
• Research Categories: Engineering, Biomedical; Chemistry, Biochemistry; Biology, Ecology

Abstract

A series of oligomeric phenols including the known natural product 3,4,3′,4′-tetrahydroxy-1,1′-biphenyl (3), the previously synthesized 2,3,8,9-tetrahydroxybenzo[c]chromen-6-one (4), and eight new related natural products, cladophorols B-I (5-12), were isolated from the Fijian green alga Cladophora socialis and identified by a combination of NMR spectroscopy, mass spectrometric analysis, and computational modeling using DFT calculations. J-resolved spectroscopy and line width reduction by picric acid addition aided in resolving the heavily overlapped aromatic signals. A panel of Gram-positive and Gram-negative pathogens used to evaluate pharmacological potential led to the determination that cladophorol C (6) exhibits potent antibiotic activity selective toward methicillin-resistant Staphylococcus aureus (MRSA) with an MIC of 1.4 μg/mL. Cladophorols B (5) and D-H (7-11) had more modest but also selective antibiotic potency. Activities of cladophorols A-I (4-12) were also assessed against the asexual blood stages of Plasmodium falciparum and revealed cladophorols A (4) and B (5) to have modest activity with EC 50 values of 0.7 and 1.9 μg/mL, respectively.